Role of TAK1 and TAB1 in BMP signaling in early Xenopus development.
Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.
Shibuya
H
H
Division of Morphogenesis, Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Japan. shibuya@nibb.ac.jp
Iwata
H
H
Masuyama
N
N
Gotoh
Y
Y
Yamaguchi
K
K
Irie
K
K
Matsumoto
K
K
Nishida
E
E
Ueno
N
N
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000187:drug effects; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000502:physiology; D004357:Drug Synergism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology; D010749:Phosphoprotein Phosphatases; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D017978:Receptors, Growth Factor; D015398:Signal Transduction / Q000235:genetics; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D014981:Xenopus / Q000196:embryology*; D029867:Xenopus Proteins; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D010749:Phosphoprotein Phosphatases; D017346:Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators; D029867:Xenopus Proteins; D000099151:MAP Kinase Kinase Kinase 7; C497402:MXD1 protein, Xenopus; C497399:SMAD1 protein, human; C497401:Smad1 protein, mouse; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human; C486301:TAB1 protein, Xenopus